DESCRIPTION (provided by investigator): This is a competing renewal of a grant in which we added on cognitive testing to two randomized clinical trials of chronic disease prevention in women: the Women's Health Study (WHS) tests low-dose aspirin and antioxidant supplementation in healthy women and the Women's Antioxidant Cardiovascular Study (WACS) tests antioxidant and folate supplementation in women with existing cardiovascular disease. These agents are also hypothesized to prevent Alzheimer disease (AD); since preventive efforts are often best focused at the earliest stages of disease development, our aim in the original application was to investigate whether these treatments might protect against early cognitive decline, a pre-clinical marker of AD risk, in community dwelling women. We conducted telephone cognitive assessments at 3 points in time over 5 years in 6,387 WHS subjects and 2,836 WACS subjects, aged 65 years and older. Both trials received NIH funding to extend follow-up by 3 years to determine whether an average 10 years on the study agents prevent cardiovascular disease or cancer; compliance and follow-up in the trials remain high after 8 years. Since cognitive decline develops slowly over a long period of time, it is likely that long durations of treatment are also necessary to prevent or delay decline. Thus, the extended follow-up of WHS and WACS provides a truly unique opportunity to extend the cognitive sub-studies too, making these among the largest and longest-term clinical trials of neuroprotection; we propose to conduct a single extra wave of cognitive testing during the final year of each trial. Using blood samples obtained from over 70 percent of participants in both trials, we will also examine interactions between these treatments and apolipoprotein E genotype. Importantly, the cognitive sub-studies have been highly successful to date, and establish: (1) effective randomization of subjects, (2) high participation and follow-up in cognitive testing and (3) that our telephone instrument is reliable, valid, and can detect expected relations with cognitive decline. In this revision, we propose to enhance our instrument by adding a 2nd test of executive function (a strong predictor of AD risk) and a test of hearing impairment. WHS has been extended until August 2004 and WACS until February 2006, thus there is a limited window of opportunity for taking advantage of the long-term follow-up.